During the next year, emphasis in the guanylate cyclase area will be placed on the (a) establishing the subcellular localization of guanylate cyclase, (b) clarifying the mechanism of the activation by detergents, (c) clarifying the mechanism of the activation by Ca ions and trying to establish whether this has physiologic significance, and (d) searching for effects of agents such as acetylcholine on guanylate cyclase activity. In addition, the purification and characterization of the extremely active guanylate cyclase from sea urchin sperm will be pursued. Factors influencing levels of cyclic GMP in tissues will be studied in several systems, especially smooth muscle, with emphasis on cholinergic agents and ions. The possible role of cyclic nucleotides in sperm motility will be investigated in sea urchin and bull sperm. Emphasis will be placed on measuring cyclic nucleotide levels in sperm in various states of motility.